Chase Geoffrey, Deng Tao, Fodor Ervin, Leung Bo Wah, Mayer Daniel, Schwemmle Martin, Brownlee George
Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.
Virology. 2008 Aug 1;377(2):431-9. doi: 10.1016/j.virol.2008.04.040.
The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses.
甲型流感病毒的病毒RNA聚合酶复合体由PB1、PB2和PA三个亚基组成。最近研究表明，细胞伴侣热休克蛋白90（Hsp90）通过与PB1和PB2结合，在三聚体聚合酶复合体的核输入和组装过程中发挥作用。在此我们发现，Hsp90抑制剂格尔德霉素或其衍生物17-AAG可延缓流感病毒在细胞培养中的生长，导致感染早期病毒滴度降低1至2个对数。我们认为，这是由于PB1和PB2半衰期缩短以及PB1和PA的核输入受到抑制，从而导致病毒核糖核蛋白（RNP）组装减少所致。Hsp90抑制剂可能代表一类新型抗流感病毒的抗病毒化合物。
